Glucose but not lactate in combination with acidosis aggravates ischemic neuronal death in vitro
| Autor: | Tadeusz Wieloch, Tobias Cronberg, Anna Söder, Anna Rytter, Fredrik Asztely |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
medicine.medical_specialty
Neurology Time Factors Ischemia Brain damage In Vitro Techniques Hippocampus Brain Ischemia chemistry.chemical_compound Mice In vivo Internal medicine medicine Animals Lactic Acid Stroke Acidosis Advanced and Specialized Nursing Neurons Mice Inbred BALB C Cell Death Dose-Response Relationship Drug business.industry Metabolic disorder Hydrogen-Ion Concentration medicine.disease Lactic acid Endocrinology Glucose chemistry Receptors Glutamate Hyperglycemia Neurology (clinical) medicine.symptom Cardiology and Cardiovascular Medicine business Excitatory Amino Acid Antagonists |
| Zdroj: | Stroke. 35(3) |
| ISSN: | 1524-4628 |
| Popis: | Background and Purpose— Hyperglycemia aggravates brain damage in clinical stroke and in experimental in vivo models of cerebral ischemia. Elevated preischemic glucose levels, lactate production, and intracerebral acidosis correlate with increased brain damage. We have developed a murine hippocampal slice culture model of in vitro ischemia (IVI), suitable for studies of the mechanisms of neuronal death. In this model we investigated the individual contribution of glucose, pH, lactate, and combinations thereof as well as ionotropic glutamate receptor activation to the development of hyperglycemic ischemic cell death. Methods— Murine organotypic hippocampal slice cultures were exposed to IVI in a medium with an ionic composition similar to that of the extracellular fluid in the brain during ischemia in vivo. Cell death was assessed by propidium iodide uptake. Ionotropic glutamate receptor blockade was accomplished by d -2-amino-5-phosphonopentanoic acid (D-APV) or 2,3-dihydro-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX). Results— The combination of high glucose levels and acidosis (pH 6.8), but not acidosis per se or the combination of lactate and acidosis during IVI, exacerbated damage. Cell death after hyperglycemic IVI was not diminished by blockade of ionotropic glutamate receptors. Conclusions— Aggravation of brain damage by hyperglycemia in vivo can be reproduced in hippocampal slice cultures in vitro. Our results demonstrate that glucose per se, but not lactate, in combination with acidosis mediates the detrimental hyperglycemic effect through a mechanism independent of ionotropic glutamate receptors. |
| Databáze: | OpenAIRE |
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